The Role of Non-Selective β-Blockers in Compensated Cirrhotic Patients without Major Complications

Abstract

Background and Objectives: Non-selective β-blockers (NSBB) could prevent decompensation and hepatocellular carcinoma (HCC) in cirrhotic patients with clinically significant portal hypertension (CSPH), but remained uncertain for compensated cirrhotic patients without major complications. We aimed to compare the clinical outcomes between propranolol users and non-users of a CC group without major complications. Material and Methods: We conducted this population-based cohort study by using the Taiwanese Longitudinal Health Insurance Database 2000. Propranolol users (classified as cumulative defined daily dose (cDDD)) and non-PPL users were matched with a 1:1 propensity score in both cohorts. Results: This study comprised 6896 propranolol users and 6896 non-propranolol users. There was no significant impact on the development of spontaneous bacterial peritonitis between the two groups (aHR: 1.24, 95% confidence interval (CI): 0.88~1.75; p = 0.2111). Male gender, aged condition, and non-liver related diseases (peripheral vascular disease, cerebrovascular disease, dementia, pulmonary disease, and renal disease) were the independent risk factors of mortality. PPL users had significantly lower incidence of HCC development than non-users (aHR: 0.81, p = 0.0580; aHR: 0.80, p = 0.1588; and aHR: 0.49, p < 0.0001 in the groups of 1–28, 29–90, and >90 cDDD, respectively). Conclusion: The current study suggested that high cumulative doses of propranolol could decrease the risk of hepatocellular carcinoma among compensated cirrhotic patients without major complications. Further large-scale prospective studies are still required to confirm the findings in this study. Results: It remained uncertain whether non-selective β-blockers (NSBB) could prevent decompensation and hepatocellular carcinoma (HCC) in compensatory cirrhotic patients without major complications. This study aimed to compare the clinical outcomes between propranolol users and non-users of the CC group without major complications.

Association Between Nonselective Beta-Blocker Use and Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Without Cirrhosis and Decompensation

“…The process of HCC manifestation in patients with HBV infection differs from that in patients with HCV infection, who mostly develop cirrhosis before HCC (Villanueva, 2019). Studies have reported a more significant protective effect on HCC incidence in patients with HCV-or alcohol-related cirrhosis than in those with HBV-related cirrhosis (Kim et al, 2012;Nkontchou et al, 2012;Herrera et al, 2016;Yeh et al, 2019). The results of our study are consistent with those of a stratified analysis of patients with HBV-associated cirrhosis (Wijarnpreecha et al, 2021).…”

“…Regarding the effect of the dose and duration on the enhancement of causality, only one study analysed the doses of NSBBs and indicated that the protective effect of NSBBs on HCC prevention was observed only in patients receiving a dose of >90 cDDD and not in low-cDDD groups (Yeh et al, 2019). Our findings revealed that the effects of NSBB use on HCC prevention cannot be extrapolated to patients with CHB even under high cumulative doses and increased durations.…”

“…Because the Asian population requires lower doses of NSBBs to reach the target blood pressure and heart rate than does the Caucasian population, the dose used on each day in this study was lower than that used in studies of the Caucasian population (Zhou et al, 1989;Hu et al, 2007). NSBB use appeared to benefit HCC prevention in the Caucasian population more than in the Asian population (Kim et al, 2012;Nkontchou et al, 2012;Herrera et al, 2016;Yeh et al, 2019;Wijarnpreecha et al, 2021).…”

“…Clinical studies have reported controversial findings regarding the role of NSBBs in HCC prevention, and most studies have recruited only patients with cirrhosis as the study population (Kim et al, 2012;Hagberg et al, 2016;Yeh et al, 2019;Wijarnpreecha et al, 2021). No study has examined the association between NSBBs and the incidence of HCC in patients with CHB who may develop HCC without cirrhosis and have a lower risk of HCC than do patients with existing cirrhosis.…”

Non-selective beta-blockers and the incidence of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis

“…This may be related to the fact that NSBBs can induce apoptosis and S-phase arrest in human HCC cell lines and reduce invasion and migration in liver cancer cells ( Işeri et al, 2014 ; Wang et al, 2018 ). A 2019 cohort study showed that high cumulative doses of propranolol reduced the risk of HCC in compensated cirrhosis patients without major complications ( Yeh et al, 2019 ). However, another study showed that the use of propranolol was associated with reduced mortality but not HCC development in patients with cirrhosis and refractory ascites ( Chen et al, 2022 ).…”